Perineva, tablets 4 mg 90 pcs

Dyspnea, Prevention of heart attacks and strokes, Angina, Hypertension (high blood pressure), Heart failure, Cardialgia (heart pain), Edema

– Arterial hypertension.

– Chronic heart failure.

– Prevention of recurrent stroke (combined therapy with indapamide) in patients who have had a stroke or transient ischemic cerebral circulation disorder.

– Stable IBS: reduction in risk of cardiovascular complications in patients with stable IBS.

Active ingredient

Composition

1 tablet 2 mg/4 mg/8 mg contains:

Active substance:

Perindopril erbumin 2,000 mg/4,000 mg/8,000 mg

Associates:

Calcium chloride hexahydrate, lactose monohydrate, crosspovidone, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate

How to take, the dosage

Overly, 1 tablet once daily, preferably in the morning, before meals.

The choice of dose should take into account the characteristics of the clinical situation (see section “Cautions”) and the degree of BP reduction during therapy.

Arterial hypertension

Perineva® can be used in monotherapy as well as in combination therapy.

The recommended starting dose is 4 mg once daily.

In patients with explicit renin-angiotensin-aldosterone system (RAAS) activity(especially with renovascular hypertension, hypovolemia and/or decreased plasma electrolytes, decompensation of CHF or severe arterial hypertension) a marked decrease in BP may develop after the first dose of the drug. At the beginning of therapy, such patients should be under close medical supervision. The recommended starting dose for such patients is 2 mg once daily.

If necessary, the dose of the drug may be increased to 8 mg once daily after one month of therapy.

At the beginning of therapy with Perineva® may develop symptomatic arterial hypotension. In patients concomitantly receiving diuretics the risk of arterial hypotension is higher due to possible hypovolemia and decreased plasma electrolytes. Caution should be exercised when using Perineva® in this group of patients. It is recommended, if possible, to stop taking diuretics 2-3 days before the expected start of therapy with Perineva® (see section “Cautions”).

If the diuretics cannot be stopped, the starting dose of Perineva® should be 2 mg daily. At the same time it is necessary to monitor renal function and serum potassium content. Further, if necessary, the dosage of Perineva® may be increased. If necessary, the use of diuretics may be resumed.

In older patients, treatment should be started with a dose of 2 mg per day. If necessary, after one month of therapy, the dose may be increased to 4 mg per day and then to a maximum dose of 8 mg per day, taking into account the state of renal function (see Table 1).

The maximum daily dose is 8 mg.

Chronic sepulmonary insufficiency

The treatment of patients with CHF with Perineva® in combination with potassium-saving diuretics and/or digoxin and/or beta-adrenoblockers is recommended to begin under close medical supervision, administering Perineva® at an initial dose of 2 mg once daily, in the morning. After 2 weeks of therapy, the dose of Perineva® may be increased to 4 mg once daily if the 2 mg dose is well tolerated and the response to therapy is satisfactory.

In patients at high risk of symptomatic arterial hypotension (e.g., patients with water-electrolyte imbalance with or without hyponatremia, patients with hypovolemia, or patients taking high-dose diuretics), if possible, before starting Perineva

sup>® should be eliminated before starting the drug Perineva®. It is recommended that BP, renal function and serum potassium levels be monitored closely before and during therapy.

Prevention of recurrent stroke (combined therapy with indapamide)

In patients with a history of cerebrovascular disease, therapy with Perineva® should be started with a daily dose of 2 mg for the first 2 weeks, then increasing the dose to 4 mg for the next 2 weeks before the use of indapamide.

The therapy should be started at any time (from 2 weeks to several years) after a stroke.

Stable CHD: Reduced risk of cardiovascular complications in patients who previously had myocardial infarction and/or coronary revascularization

In patients with stable CHD, therapy with Perineva® should be started with a dose of 4 mg once daily.

In 2 weeks with good tolerance of the drug and taking into account the state of renal function, the dose can be increased up to 8 mg once daily.

Patients of advanced age should start therapy with a dose of 2 mg once daily for the first week, then 4 mg once daily for the next week. Then, taking into account the state of renal function, the dose may be increased to 8 mg once daily (see Table 1). Increase the dose of the drug only if it is well tolerated in the previously recommended dose.

Special patient groups

Renal failure

. In patients with renal impairment, the dose of Perineva® should be adjusted for creatinine clearance (CK).

Table 1. Dosage of the drug Perineva® in renal failure

QC (ml/min)

Recommended dose

≥ 60

4 mg per day

? 30 and < 60

2 mg per day

? 15 and < 30

2 mg every other day

< 15 (patients on hemodialysis*)

2 mg per day of dialysis

Interaction

Simultaneous use is contraindicated

. Concomitant use of ACE inhibitors with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate to severe renal function impairment (GFR less than 60 ml/min/1.73 m2 body surface area). Concomitant use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy. Extracorporeal methods of treatment.

Neutral endopeptidase inhibitors

an increased risk of angioedema has been reported when ACE inhibitors are used simultaneously with neutral endopeptidase inhibitors such as sacubitril and racecadotril (enkephalinase inhibitor).

The simultaneous use of ACE inhibitors with medicinal products containing sacubitril (neprolizine inhibitor) increases the risk of angioedema, therefore simultaneous use of these drugs is contraindicated. ACE inhibitors should be administered not earlier than 36 hours after withdrawal of drugs containing Sacubitril. Administration of the drugs containing Sacubitril is contraindicated in patients receiving ACE inhibitors and also within 36 hours after withdrawal of ACE inhibitors.

Drugs that cause hyperkalemia

Some drugs or drugs in other pharmacological classes may increase the risk of hyperkalemia: aliskiren and aliskiren-containing drugs, potassium salts, potassium-saving diuretics, ACE inhibitors, ARA II, nonsteroidal anti-inflammatory drugs (NSAIDs), heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim, co-trimoxazole (trimethoprim + sulfamethoxazole). The combination of these drugs increases the risk of hyperkalemia.

Double RAAS blockade

The literature has reported that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concurrent therapy with an ACE inhibitor and ARA II is associated with higher rates of arterial hypotension, syncope, hyperkalemia, or impaired renal function (including ARF) compared with use of the RAAS-acting drug alone. Concomitant use of ACE inhibitors with aliskiren and drugs containing aliskiren is not recommended in patients without diabetes mellitus and/or without moderate or severe renal impairment (and contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area). Concomitant use of ACE inhibitors with APA II is not recommended in patients without diabetic nephropathy (and contraindicated in patients with diabetic nephropathy).

Simultaneous use is not recommended

(see also “Cautionary Notes. Also see “Cautionary Note”)

Aliskiren

In patients without a history of diabetes mellitus and/or moderate renal dysfunction, there may be an increased risk of hyperkalemia, impaired renal function, and increased incidence of cardiovascular morbidity and mortality.

Extracorporeal therapies

Extracorporeal treatments that bring blood into contact with negatively charged surfaces, such as dialysis or hemofiltration with certain high-flow membranes (e.g., polyacrylonitrile membranes) and LDL apheresis with dextran sulfate increase the risk of severe anaphylactoid reactions. If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of hypotensive agent.

Estramustine

Concomitant use may increase the risk of angioedema.

Racecadotril (encephalinase inhibitor used to treat acute diarrhea)

The risk of angioedema increases when ACE inhibitors are used concurrently with racecadotril.

Cyclosporine

Concurrent use with ACE inhibitors may increase the risk of hyperkalemia. Monitoring of serum potassium is recommended.

Heparin

Hyperkalemia may occur when ACE inhibitors are used simultaneously with heparin. Monitoring of serum potassium is recommended.

Co-trimoxazole (trimethoprim + sulfamethoxazole)

Trimethoprim is known to act as a potassium-saving diuretic (such as amiloride). Therefore, concomitant use with perindopril is not recommended.

Inhibitors mTOR (mammalian Target of

Special Instructions

(see also sections “Interaction with other medicinal products”, “Cautions”)

Bilateral stenosis of the renal arteries, presence of only one functioning kidney, renal failure, systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.).), therapy with immunosuppressants, allopurinol, procainamide (risk of neutropenia, agranulocytosis), reduced circulating blood volume (CBC) (taking diuretics, salt-free diet, vomiting, diarrhea), angina pectoris, cerebrovascular disease, Renovascular hypertension, diabetes mellitus, CHF class IV according to NYHA classification, simultaneous use of potassium-saving diuretics, potassium preparations, and potassium-containing salt substitutes, lithium preparations, hyperkalemia, surgery/general anesthesia, hemodialysis using high-flow membranes, desensitization therapy, low-density lipoprotein (LDL) apheresis, Post kidney transplantation, aortic stenosis/mitral stenosis/hypertrophic obstructive cardiomyopathy (HACMI), use in non-hybrid patients, congenital glucose-6-phosphate dehydrogenase deficiency.

Perineva® should not be used in children and adolescents less than 18 years of age because there are no data on the efficacy and safety of perindopril in patients in this age group.

In Elderly patients treatment should be started with a dose of 2 mg daily. If necessary, after one month of therapy, the dose may be increased to 4 mg per day and then to a maximum dose of 8 mg per day, taking into account the state of renal function (see Table 1).

The maximum daily dose is 8 mg.

Renal Impairment

In patients with renal impairment, the dose of Perineva® should be adjusted for creatinine clearance (CK).

Table 1. Dosage of the drug Perineva® in renal failure

QC (ml/min)

Recommended dose

≥ 60

4 mg per day

? 30 and < 60

2 mg per day

? 15 and < 30

2 mg every other day

< 15 (patients on hemodialysis*)

2 mg per day of dialysis

Synopsis

Tablets 2 mg. Round, slightly biconvex, white or almost white, beveled tablets.

Tablets 4 mg. Oval, slightly biconvex tablets, white or almost white, beveled, with a rib on one side.

Tablets 8 mg. Round, slightly biconvex tablets white or almost white, beveled, with a rib on one side.

Contraindications

– Hypersensitivity to the active substance, other ACE inhibitors and excipients (see section “Composition”) included in the drug.

– Lactase deficiency, lactose intolerance, glucose-galactose deficiency syndrome (Perineva® contains lactose).

– Hereditary/idiopathic angioedema.

– History of angioedema (Quincke’s edema) associated with ACE inhibitor use.

– Significant bilateral renal artery stenosis or artery stenosis of the only functioning kidney.

– Concurrent use with aliskiren and drugs containing aliskiren in patients with diabetes and/or with moderate to severe renal function impairment (GFR < 60 ml/min/1.73 m2 body surface area) (see

Sections “Special Precautions” and “Interaction with other medicinal products”).

– Concurrent use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.

– Concomitant use with neutral endopeptidase inhibitors (e.g., with drugs containing sacubitril) due to the high risk of angioedema.

– Extracorporeal treatments that bring blood into contact with negatively charged surfaces.

– Pregnancy (see “Administration during pregnancy and breastfeeding”).

– The period of breast-feeding (see section “Administration during pregnancy and breast-feeding”).

– Age under 18 years (effectiveness and safety not established).

Side effects

The safety profile of perindopril is consistent with that of ACE inhibitors.

The most common adverse events reported in clinical trials and observed with perindopril are: Dizziness, headache, paresthesia, vertigo, visual disturbances, tinnitus, marked decrease in BP, cough, shortness of breath, abdominal pain, constipation, diarrhea, impaired taste, dyspepsia, nausea, vomiting, skin itching, skin rash, muscle spasm and asthenia.

World Health Organization (WHO) recommended side effect frequency classification:

very frequently ≥1/10

often ≥ 1/100 to < 1/10

infrequently from ≥ 1/1000 to < 1/100

rarely from ≥ 1/10000 to < 1/1000

very rarely < 1/10000

frequency is unknown cannot be estimated from available data.

Disorders with the blood and lymphatic system:

infrequently*: eosinophilia;

very rarely: decrease in hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency (see See section “Special Indications”).

Metabolic and nutritional disorders:

not infrequently*: hypoglycemia (see Interaction with other medicinal products” and “Cautions”), hyperkalemia, reversible after discontinuation of the drug (see “Cautions”), hyponatremia.

Nervous system disorders:

often: paresthesia, headache, dizziness, vertigo;

infrequent: drowsiness*, fainting*;

very rare: confusion.

Mental disorders:

infrequent: sleep disturbances, mood lability.

Visual disorders:

often: visual disturbances.

Hearing organ and labyrinth disorders:

often: tinnitus.

Disorders with the heart:

infrequently*: tachycardia, palpitations;

very rarely: cardiac rhythm disturbances, angina pectoris, myocardial infarction, possibly due to marked BP reduction in high-risk patients (see See section “Special Indications”).

Disorders with vascular disorders:

often: severe decreased BP and related symptoms;

infrequently*: vasculitis;

very rarely: stroke, possibly due to marked BP reduction in high-risk patients (see

frequent unknown: Raynaud’s syndrome.

Disorders of the respiratory system, thorax and mediastinum:

often: cough, shortness of breath;

infrequent: bronchospasm;

very rare: eosinophilic pneumonia, rhinitis.

Disorders of the digestive system:

often: constipation, nausea, vomiting, abdominal pain, taste disorder, dyspepsia, diarrhea;

infrequently: dry oral mucosa;

very rarely: pancreatitis.

Hepatic and biliary tract disorders:

very rarely: hepatitis (cholestatic or cytolytic) (see section “Special indications”).

Skin and subcutaneous tissue disorders:

often: skin itching, skin rash;

infrequently: Angioneurotic edema of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal folds and/or larynx, urticaria (see

rarely: exacerbation of psoriasis*;

very rarely: erythema multiforme.

Musculoskeletal and connective tissue disorders:

often: muscle spasm;

infrequently*: arthralgia, myalgia.

Renal and urinary tract disorders:

infrequent: renal failure;

very rare: acute renal failure (ARF).

Gender and mammary gland disorders:

infrequent: erectile dysfunction.

General disorders and disorders at the site of administration:

often: asthenia;

infrequently: chest pain*, peripheral edema*, weakness*, fever*, falls*.

Laboratory and instrumental findings:

infrequent*: Increased plasma urea and creatinine concentrations;

rarely: increased “hepatic” transaminase activity and serum bilirubin concentrations.

*Evaluation of the incidence of adverse reactions identified by spontaneous reports has been performed on the basis of data from clinical trials.

The incidence of inadequate antidiuretic hormone secretion syndrome (ADHSS) has been reported with other ACE inhibitors. Inadequate ADH secretion syndrome can be considered a very rare but possible complication associated with therapy with ACE inhibitors, including perindopril.

adverse events reported in clinical trials

Only serious adverse events were reported in the clinical trial. Serious adverse events were reported in patients in the perindopril group and in patients in the placebo group. In perindopril group, marked BP decrease, angioneurotic edema, and sudden cardiac arrest were noted in patients. The frequency of perindopril withdrawal due to cough, marked BP decrease, or other intolerance was higher in the perindopril group compared to the placebo group.

Overdose

There are limited data on overdose of the drug.

Symptoms

Developed BP decrease, shock, water-electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough.

Treatment

Emergency measures are limited to elimination of the drug from the body: gastric lavage and/or administration of activated charcoal followed by restoration of water-electrolyte balance.

In case of a pronounced BP decrease, the patient should be transferred to the “lying” position on his back with his legs elevated. If necessary, 0.9% sodium chloride solution should be administered intravenously (IV). If necessary, catecholamine solution may be administered intravenously. Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis. If bradycardia resistant to therapy develops, implantation of a pacemaker may be required. Essential vital signs, creatinine concentration and serum electrolytes should be monitored continuously.

Pregnancy use

Pregnancy

Perineva® is contraindicated in pregnancy (see section “Contraindications”).

If pregnancy is planned or occurs during the use of Perineva®, the drug should be stopped immediately and, if necessary, other hypotensive therapy with a proven safety profile in pregnancy should be prescribed.

It is known that exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy may lead to impaired fetal development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient received ACE inhibitors in the second or third trimester of pregnancy, an ultrasound examination of the newborn is recommended to assess cranial bone condition and renal function.

Breastfeeding period

It is not known whether perindopril penetrates into breast milk. Therefore, the use of Perineva® during breastfeeding is contraindicated.

If the use of Perineva® is necessary while breastfeeding, breastfeeding must be stopped.

Fertility

Preclinical studies have shown no effect of perindopril on fertility in rats of either sex.

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